The biochemistry group has a dual role in this program project. It is responsible for the initial biochemical characterization of agents synthesized under this grant, and also performs in-depth biochemical routine determinations and hence appears appropriate for support as a core. Our proposed core consists of (a) a cell culture laboratory that determines cytotoxicities of new agents, collaborates with the biochemists in the performance of routine metabolic experiments in cell culture, and provides cells in quantity for enzyme isolations, and (b) a component for rapidly obtaining a biochemical profile of a new agent by subjecting it to a series of assays including examination by HPLC of its phosphorylation and its effects on nucleotide pools, determinations of its effects on macromolecular syntheses, and determination of its activity as substrate or inhibitor of selected enzymes of nucleoside metabolism.